Transport of water in and out of a cell in the brain is regulated by a transmembrane water channel which is referred to as the aquaporin family formed of an aquaporin (AQP) and an aquaglyceroporin. An aquaporin 4 (AQP 4) is one of the aquaporin families with extremely high water selectivity and is a main AQP associated with the transport of water in the brain. Further, a large amount of the AQP 4 is present in the brain, particularly in an end-feet membrane of astrocytes in contact with a basement membrane.
A perivascular space between blood vessels and brain tissues which are distributed in the brain is referred to as a “Virchow-Robin space” that is named after the discoverer. In recent years, it has been suggested that waste matter in protein decomposition products and other cells is transported through the Virchow-Robin space so as to be reabsorbed in the vena cava and flows into the cerebrospinal fluid (CSF) in the brain ventricle. This transporation is similar to a lymphatic system, and a system that discharges waste matter from the brain through the Virchow-Robin space is referred to as a glymphatic system.
It was found that the ability of discharging water into the brain ventricle through first and second perivascular spaces is weak in a case of mice in which the AQP 4 is genetically deleted and the glymphatic system is dependent on the expression level of the AQP 4 (for example, see Non-Patent Document 1).
Further, amyloid β protein (Aβ) serving as a main constituent component of senile plaques which are one of the pathological features of Alzheimer's disease and a by-product produced when cutting the amyloid β protein are known to be discharged through the glymphatic system. It was suggested that the ability of discharging water into the brain ventricle through first and second perivascular spaces is weak in a case of Alzheimer's disease model gene-modified mice and Aβ is accumulated (for example, see Non-Patent Document 2).
In addition, it was suggested that the flow of waste matter from the perivascular space into the CSF is significantly decreased in the brains of the Alzheimer's disease patients (for example, see Non-Patent Document 3).
Accordingly, it can be expected to delay the onset and progression of Alzheimer's disease by promoting transport of water using the AQP 4 in the brain so that the flow of the CSF that weakens with age and the discharge function using the glymphatic system are promoted.
Patent Document 1 describes an aquaporin function enhancer containing hyaluronic acid as an active ingredient used for the purpose of enhancing mainly the function of the AQP 2 or AQP 3.